Mitochondrial Dysfunction and Heart Disease: Critical Appraisal of an Overlooked Association

• Main Authors: Giandomenico Bisaccia, Fabrizio Ricci, Sabina Gallina, Angela Di Baldassarre, Barbara Ghinassi
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: mitochondria; heart failure; mitochondrial dynamics; cardiomyopathy; cardiac energetics
• Online Access: https://www.mdpi.com/1422-0067/22/2/614

The myocardium is among the most energy-consuming tissues in the body, burning from 6 to 30 kg of ATP per day within the mitochondria, the so-called powerhouse of the cardiomyocyte. Although mitochondrial genetic disorders account for a small portion of cardiomyopathies, mitochondrial dysfunction is commonly involved in a broad spectrum of heart diseases, and it has been implicated in the development of heart failure via maladaptive circuits producing and perpetuating mitochondrial stress and energy starvation. In this bench-to-bedside review, we aimed to (i) describe the key functions of the mitochondria within the myocardium, including their role in ischemia/reperfusion injury and intracellular calcium homeostasis; (ii) examine the contribution of mitochondrial dysfunction to multiple cardiac disease phenotypes and their transition to heart failure; and (iii) discuss the rationale and current evidence for targeting mitochondrial function for the treatment of heart failure, including via sodium-glucose cotransporter 2 inhibitors.